The presence of radioresistant hypoxic cells within solid tumors may contribute to the treatment failure of conventional radiotherapy and some forms of chemotherapy. Cells can survive up to 15 hours of the most severe oxygen deprivation without any change in viability.
It has previously been shown that hypoxic cells undergo changes in cellular metabolism and gene regulation, but little data exists to demonstrate that these changes are responsible for promoting increased survival of those cells in these environmental conditions. In addition, the increased synthesis of some proteins by such cells may not necessarily be harmful, but may be a consequence of cellular organelle damage.
Since poor vascularization is often associated with solid tumors, regions of a tumor containing hypoxic cells are expected. As just noted, these regions may be more resistant to radiotherapy, which is mediated to a certain extent by oxygen-radical damage, and to traditional types of chemotherapy, for example, because of reduced rates of cell division.
It is desirable then to augment these forms of tumor therapy with ones that are able to produce selective cell killing in tumor regions of hypoxic cells. Heretofore, at least one therapy of this type has been proposed--hyperthermic treatment of tumor cells. This approach relies on the reduced circulation in poorly vascularized or vaso-occluded tumor regions (and therefore regions of hypoxic cells) to selectively heat and kill cells when the tumor is heated, for example, by infrared radiation.
The present invention provides another, and generally more versatile, approach to selective killing of regions of hypoxic cells in solid tumors.